[Clinical trials considerations for patients with immune-tolerant phase chronic hepatitis B].

Most patients with early stage chronic hepatitis B virus infection are in the immune-tolerant phase. Therefore, previously been generally believed that there is no disease progression or liver injury-related events, and poor antiviral efficacy in patients with immune-tolerant phase. With that in mind, antiviral therapy is generally not recommended in current domestic and foreign guidelines. However, more and more studies have shown that patients in the immune-tolerant phase may develop liver cirrhosis and hepatocellular carcinoma without treatment, so clinical treatment is urgently needed. Currently, drugs based on nucleocapsid inhibitor, immune modulation, and other novel mechanisms for viral replication are being developed to reduce hepatitis B surface antigen, which offers the possibility to achieve viral suppression or even functional cure in these patients. This paper mainly reviews and discusses the latest research progress, population characteristics, treatment needs, and design strategies of clinical trials of new drug for immune-tolerant phase population.

Haploidentical transplantation for pediatric patients with acquired severe aplastic anemia.

Techniques for haploidentical hematopoietic stem cell transplantation (haplo-HSCT) to treat severe aplastic anemia (SAA) have recently improved, but no protocol has been evaluated in a large number of pediatric patients. Fifty-two children with SAA received haplo-HSCT in our center. The treatment protocol used G-CSF-primed bone marrow with G-CSF-mobilized PBSCs without in vitro T-cell depletion. The conditioning regimen included busulfan/cyclophosphamide and antithymocyte globulin. Fifty-one patients achieved primary engraftment; one child died of regimen-related toxicity on the day +1. Secondary graft failure occurred in three patients. The cumulative incidences of aGVHD grade II-IV and grade III-IV were 39.2±0.5 and 13.7±0.2%, respectively. The cumulative incidence of cGVHD was 34.2±0.5%. The 3-year overall and failure-free survival rates were 84.5±5.0 and 82.7±5.2%, respectively, with a median follow-up time of 744.5 days (100-3294) for surviving patients. The Eastern Cooperative Oncology Group score was the only predictor of overall and failure-free survival rates. Clinical outcomes were similar between the upfront and salvage group. This result suggests that both newly diagnosed and refractory pediatric SAA patients benefit from haplo-HSCT, especially when patients are in good general condition. Therefore, haplo-HSCT might be an alternative therapy for pediatric SAA patients without HLA-matched sibling donors.